Is DRC2 p.Arg472His (c.1415G>A) pathogenic?

DRC2 p.Arg472His (c.1415G>A) is classified Benign/Likely benign in DRC2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0761); Common (popmax 8.71%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Arg472His (c.1415G>A)?

DRC2 p.Arg472His (c.1415G>A) is associated with primary ciliary dyskinesia 27 (ClinVar).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DRC2 p.Arg472His (c.1415G>A)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

DRC2 p.Arg472His

Q: How common is DRC2 p.Arg472His (c.1415G>A) in the general population?

DRC2 p.Arg472His (c.1415G>A) is common (popmax 8.71%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1415G>A · rs80052257 · VCV416602

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.71%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 27

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP 0.12
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	13.93	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.71% African / African-American · 6,531/74,942 alleles

Filtering AF 8.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.47%

Overall 0.473% 7,634/1,613,282 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.71%	11
Remaining individualsnot grpmax-eligible	0.692%	145
Admixed American	0.68%	147
Middle Eastern	0.462%	216
South Asian	0.0187%	5,357
European (non-Finnish)	0.0184%	5,435
East Asian	0.00223%	44,870

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DRC2
Protein: p.Arg472His
Coding: c.1415G>A
MANE Select: NM_033124
dbSNP: rs80052257
Type: single nucleotide variant
Location: chr12:48921403 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DRC2 p.Arg472Cys Uncertain significance ★★ ⚠ same residue
CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same condition
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala109Val Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala114Pro Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg118Cys Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg294His Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/drc2-p-arg472his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown